Maternal Antenatal Complications and the Risk of Neonatal Cerebral White Matter Damage and Later Cerebral Palsy in Children Born at an Extremely Low Gestational Age

Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
American journal of epidemiology (Impact Factor: 5.23). 09/2009; 170(7):819-28. DOI: 10.1093/aje/kwp206
Source: PubMed


In a 2002-2004 prospective cohort study of deliveries of infants at <28 weeks at 14 US centers, the authors sought the antecedents of white matter damage evident in newborn cranial ultrasound scans (ventriculomegaly and an echolucent lesion) and of cerebral palsy diagnoses at age 2 years. Of the 1,455 infants enrolled, those whose mothers received an antenatal steroid tended to have lower risks of ventriculomegaly and an echolucent lesion than their peers (10% vs. 23%, P < 0.001 and 7% vs. 11%, P = 0.06, respectively). Risk of ventriculomegaly was increased for infants delivered because of preterm labor (adjusted odds ratio (OR) = 2.3, 95% confidence interval (CI): 1.1, 4.9), preterm premature rupture of fetal membranes (OR = 3.6, 95% CI: 1.5, 8.7), and cervical insufficiency (OR = 2.8, 95% CI: 1.4, 5.5) when compared with infants delivered because of preeclampsia. Risk of an echolucent lesion was increased for infants delivered because of preterm labor (OR = 2.7, 95% CI: 1.2, 5.7) and intrauterine growth retardation (OR = 3.3, 95% CI: 1.2, 9.4). The doubling of diparesis risk associated with preterm labor and with preterm premature rupture of fetal membranes did not achieve statistical significance, nor did the doubling of quadriparesis risk and the tripling of diparesis risk associated with cervical insufficiency.

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    • "PROM has been associated with increased risk for intrauterine infection and clinical chorioamnionitis [43,44], and it has been observed that infants born after PROM are at increased risk of white matter injury and subsequent CP diagnosis [45,46]. In our study, we found that the genotypes of SNPs rs1800796 and rs2066992 are associated with CP and that this association is more robust in CP patients with maternal PROM. "
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    ABSTRACT: Background The relationship between genetic factors and the development of cerebral palsy (CP) has recently attracted much attention. Polymorphisms in the genes encoding proinflammatory cytokines have been shown to be associated with susceptibility to perinatal brain injury and development of CP. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a pivotal role in neonatal brain injury, but conflicting results have been reported regarding the association between IL-6 single nucleotide polymorphisms (SNPs) and CP. The purpose of this study was to analyze IL-6 gene polymorphisms and protein expression and to explore the role of IL-6 in the Chinese CP population. Methods A total of 753 healthy controls and 713 CP patients were studied to detect the presence of five SNPs (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL-6 locus. Of these, 77 healthy controls and 87 CP patients were selected for measurement of plasma IL-6 by Luminex assay. The SHEsis program was used to analyze the genotyping data. For all comparisons; multiple testing on each individual SNP was corrected by the SNPSpD program. Results There were no differences in allele or genotype frequencies between the overall CP patients and controls among the five genetic polymorphisms. However, subgroup analysis found significant sex-related differences in allele and genotype frequencies. Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837. Plasma IL-6 levels were higher in CP patients than in the controls, and this difference was more robust in full-term male spastic CP patients. Furthermore, the genotype has an effect on IL-6 synthesis. Conclusions The influence of IL-6 gene polymorphisms on IL-6 synthesis and the susceptibility to CP is related to sex and gestational age.
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    Proceedings of the 2002 International Symposium on Low Power Electronics and Design, 2002, Monterey, California, USA, August 12-14, 2002; 01/2002
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    ABSTRACT: The pathological picture in ischemic tissue injury shares features with the inflammatory response. Hypoxia-mediated induction of interleukin-6 (IL-6) could set in motion the mechanisms limiting inflammation in ischemia. Intrauterine growth restriction (IUGR) represents a human model of chronic fetal hypoxia. The purpose of this study was a first-time exploration to determine whether cord blood obtained at the delivery of small-for-gestational-age (SGA) infants has increased concentrations of inflammatory markers. Cord blood was collected from 20 SGA (term and near-term) infants and 20 appropriate-for-gestational-age (AGA) controls. Infants exposed to maternal smoking, diabetes, maternal chronic diseases, or alcohol or drug use were excluded. Both groups had Apgar score ≥7 at 1 min with a normal cord pH (>7.25). Cord-serum cytokines and thrombopoietin (TPO) levels were measured by enzyme linked immunosorbent assay. C-reactive protein (CRP) was measured using a turbidometric immunoassay. SGA infants had a significantly smaller birth weight than AGA controls, with a smaller gestation age by 1 week. There were significant elevations in IL-6, tumor necrosis factor (TNF-α), CRP and TPO in the SGA compared with the AGA group, which persisted in multiple regression analysis even after gestational age was taken into account. As hypothesized, significant increases in the cord blood concentrations of known inflammatory markers were found in SGA infants compared with the controls.
    Journal of perinatology: official journal of the California Perinatal Association 01/2011; 31(1):30-2. DOI:10.1038/jp.2010.53 · 2.07 Impact Factor
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